rs1557072752

chrX-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_006280.3(SSR4):c.187-301_352-15del variant causes a splice acceptor, splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 24)
• Consequence: SSR4 NM_006280.3 splice_acceptor, splice_donor, splice_donor_5th_base, coding_sequence, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.06

Genes affected

SSR4 (HGNC:11326): (signal sequence receptor subunit 4) This gene encodes the delta subunit of the translocon-associated protein complex which is involved in translocating proteins across the endoplasmic reticulum membrane. The encoded protein is located in the Xq28 region and is arranged in a compact head-to-head manner with the isocitrate dehydrogenase 3 (NAD+) gamma gene and both genes are driven by a CpG-embedded bidirectional promoter. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.14176245 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PP5: Variant X-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G is Pathogenic according to our data. Variant chrX-153797128-GGGCACCCCTGACCCCAGCACCTCCCTTGTAGACTCAGGAAATCACTCAGCCCTTTTGATCATCCCGCCCCTGCTCACAGTCAACAGGGTTCCTATGCGTCCAGTTAGGCCCGGCCATGGGGATCTGGCCTTGTGCCCCCGTAGGGAAGACCAATGCAGAGGGCCAGTCACGGGATTGGTGAGTGTTACTTGGTACCTCCTGCCAGGGACACTGCAGCCCCCAACTGGGCCTAGCCTGCCCACCTGCAGGCCGTGTGAGCAGCGCACAGGGCTCCTCTGCCCACACCCAGAGGGGGCAGAAGGTGACCCTGCCTTTGTTCCCTCACCCAGAACATGGCTCTCTATGCTGACGTCGGTGGAAAACAATTCCCTGTCACTCGAGGCCAGGATGTGGGGCGTTATCAGGTGAGGGGCCAATGGTTCCCTTGCTAGGGGGCTCCCTGCTCCCGGGTGTGACCTGAAGCCCCAGGGGTGGCCGGTCAACCAGGGCCAGGGGCCGTGGGCTCTGGCTGCCGGAGTGCTGCAGTGTCGGCACTGGTGGTCAGGGTGGCCCCTCCGTGTCCACTCTGCCCACACTCTGCTCAACACCCAACCCAGGTGTCCTGGAGCCTGGACCACAAGAGCGCCCACGCAGGCACCTATGAGGTTAGATTCTTCGACGAGGAGTCCTACAGCCTCCTCAGGAAGGTGAGGACTCCTGTAGCCCACTGTGCTCCCCTGTCCCTGGGGAGCAGGATGGGCTGGGTTGGGAGGTGCTGGCAGCAAGTCCTGAGCTGGGTGGCCTTTCTGTGATCCTGTCCCTTCCTCAGTGTCTCTTGCCCATTTCTCTCCTTTCCTTTTCTGGGGCTTGGGCCGGTGTTCCTACCTGTCTTTCCCCTCCCCTCCCCACCCCCACACGCCA-G is described in ClinVar as [Pathogenic]. Clinvar id is 372143.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSR4	NM_006280.3	c.187-301_352-15del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	3/6	ENST00000370086.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSR4	ENST00000370086.8	c.187-301_352-15del		splice_acceptor_variant, splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	3/6	1	NM_006280.3	P1

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

SSR4-congenital disorder of glycosylation Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 28, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1557072752; hg19: chrX-153062583;